Florini Francesca, Visone Joseph E, Hadjimichael Evi, Malpotra Shivali, Nötzel Christopher, Kafsack Björn F C, Deitsch Kirk W
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
bioRxiv. 2024 Mar 9:2024.03.08.584127. doi: 10.1101/2024.03.08.584127.
Chronic, asymptomatic malaria infections contribute substantially to disease transmission and likely represent the most significant impediment preventing malaria elimination and eradication. parasites evade antibody recognition through transcriptional switching between members of the gene family, which encodes the major virulence factor and surface antigen on infected red blood cells. This process can extend infections for up to a year; however, infections have been documented to last for over a decade, constituting an unseen reservoir of parasites that undermine eradication and control efforts. How parasites remain immunologically "invisible" for such lengthy periods is entirely unknown. Here we show that in addition to the accepted paradigm of mono-allelic gene expression, individual parasites can simultaneously express multiple genes or enter a state in which little or no gene expression is detectable. This unappreciated flexibility provides parasites with greater adaptive capacity than previously understood and challenges the dogma of mutually exclusive gene expression. It also provides an explanation for the antigenically "invisible" parasites observed in chronic asymptomatic infections.
慢性无症状疟疾感染对疾病传播有很大影响，可能是阻止疟疾消除和根除的最重大障碍。疟原虫通过基因家族成员之间的转录转换来逃避抗体识别，该基因家族编码感染红细胞上的主要毒力因子和表面抗原。这一过程可使感染持续长达一年；然而，有记录显示感染可持续十多年，构成了一个看不见的疟原虫库，破坏了根除和控制工作。疟原虫如何在如此长的时间内保持免疫“隐形”完全未知。在这里，我们表明，除了公认的单等位基因表达模式外，单个疟原虫可以同时表达多个基因，或者进入几乎检测不到基因表达的状态。这种未被认识到的灵活性赋予疟原虫比以前所理解的更大的适应能力，并挑战了互斥基因表达的教条。这也为在慢性无症状感染中观察到的抗原性“隐形”疟原虫提供了解释。
